Ankyrin-B is required for intracellular sorting of structurally diverse Ca2+ homeostasis proteins.
Ankyrin-B is required for intracellular sorting of structurally diverse Ca2+ homeostasis proteins.
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DOI：
10.1083/jcb.147.5.995
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发表时间：
1999-11-29
期刊：
影响因子：
--
通讯作者：
Bennett V
中科院分区：
文献类型：
--
作者：
Tuvia S;Buhusi M;Davis L;Reedy M;Bennett V
本报告描述了一种先天性肌病和主要损失的胸腺淋巴细胞在ankle-B（−/−）小鼠以及戏剧性的改变细胞内定位的关键组成部分的钙离子稳态机制ankle-B（−/−）横纹肌和胸腺。基于电子显微镜和三聚体和二氢吡啶受体的正常模式的存在，囊质网（SR）和SR/T-小管连接在强直性脊柱炎-B（−/−）骨骼肌中明显保持正常分布。因此，SR/ER Ca ATP酶（SERCA）和兰尼碱受体的异常定位代表了骨骼肌中这些蛋白质的细胞内分选缺陷。这些观察结果的外推表明，靶向缺陷是兰尼碱受体、IP 3受体和SERCA在心脏中以及IP 3受体在anke-B（−/−）小鼠胸腺中异常定位的基础。220-kD锚蛋白-B的表达挽救了锚蛋白-B（-/-）心肌细胞中SERCA 2和ryanodine受体2的错误分选，表明缺乏220-kD锚蛋白-B多肽是这些细胞中的主要缺陷。锚蛋白-B与细胞内囊泡相关，但不与骨骼肌中的大部分SERCA 1或ryanodine受体1共定位。这些数据提供了在横纹肌和免疫系统的钙稳态机制的细胞内靶向中对锚蛋白-B的生理需求的第一个证据，并且此外，支持不涉及锚蛋白-B和靶蛋白之间的永久化学计量复合物的催化作用。锚蛋白-B是衔接蛋白家族的一员，参与将不同蛋白质限制到专门的质膜结构域。类似的机制，涉及锚蛋白可能是必要的功能定义的蛋白质内的质膜的专门区域和内的Ca 2+稳态区室的ER的隔离。
This report describes a congenital myopathy and major loss of thymic lymphocytes in ankyrin-B (−/−) mice as well as dramatic alterations in intracellular localization of key components of the Ca2+ homeostasis machinery in ankyrin-B (−/−) striated muscle and thymus. The sacoplasmic reticulum (SR) and SR/T-tubule junctions are apparently preserved in a normal distribution in ankyrin-B (−/−) skeletal muscle based on electron microscopy and the presence of a normal pattern of triadin and dihydropyridine receptor. Therefore, the abnormal localization of SR/ER Ca ATPase (SERCA) and ryanodine receptors represents a defect in intracellular sorting of these proteins in skeletal muscle. Extrapolation of these observations suggests defective targeting as the basis for abnormal localization of ryanodine receptors, IP3 receptors and SERCA in heart, and of IP3 receptors in the thymus of ankyrin-B (−/−) mice. Mis-sorting of SERCA 2 and ryanodine receptor 2 in ankyrin-B (−/−) cardiomyocytes is rescued by expression of 220-kD ankyrin-B, demonstrating that lack of the 220-kD ankyrin-B polypeptide is the primary defect in these cells. Ankyrin-B is associated with intracellular vesicles, but is not colocalized with the bulk of SERCA 1 or ryanodine receptor type 1 in skeletal muscle. These data provide the first evidence of a physiological requirement for ankyrin-B in intracellular targeting of the calcium homeostasis machinery of striated muscle and immune system, and moreover, support a catalytic role that does not involve permanent stoichiometric complexes between ankyrin-B and targeted proteins. Ankyrin-B is a member of a family of adapter proteins implicated in restriction of diverse proteins to specialized plasma membrane domains. Similar mechanisms involving ankyrins may be essential for segregation of functionally defined proteins within specialized regions of the plasma membrane and within the Ca2+ homeostasis compartment of the ER.
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DOI：
10.1016/s0167-4889(98)00054-8
发表时间：
1998-08-14
影响因子：
5.1
作者：
Beck, KA;Nelson, WJ
通讯作者：
Nelson, WJ
影响因子：
7.8
作者：
Henkart, M;Landis, D M;Reese, T S
通讯作者：
Reese, T S
影响因子：
4.8
作者：
Michaely, P;Bennett, V
通讯作者：
Bennett, V
影响因子：
--
作者：
CRAIG, SW;PARDO, JV
通讯作者：
PARDO, JV
DOI：
10.1083/jcb.136.5.1059
发表时间：
1997-03-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hoock TC;Peters LL;Lux SE
通讯作者：
Lux SE